The goals of this research are to discover new intramolecular cycloadditions, to examine the scope and limitations of these reactions, and to develop ways to predict the rates and stereoselectivities of intramolecular cycloadditions. In the previous grant periods, intramolecular [6+4], [6+2], [8+2], and [8+6] cycloadditions were discovered, and systematic studies of these reactions were begun. In the most recent grant period, the [6+2] cycloaddition was used for a formal capnellene synthesis, and as an approach to hirsutene. Considerable progress was also made toward the development of force fields for the prediction of several types of thermal and photochemical cycloadditions. This proposal requests support for further experimental investigations of new cycloadditions, and expansion of the theoretical inquiries into the realm of understanding of the rates and selectivities of intramolecular reactions in general. Experimental studies will test the predictions of the theoretical calculations. New reactions to be investigated include intramolecular cycloadditions involving fulvenes to form tricyclopentanoids and other ring systems, and intramolecular [6+4] cycloadditions of fulvenes, and other new [6+4] cycloadditions. The cycloadditions of s-trans polyenes will also be attempted. Theoretical studies will continue, and force fields will be developed or perfected for intramolecular Diels-Alder reactions, intramolecular nitrile oxide cycloadditions, intramolecular ketene cycloadditions, intramolecular ene reactions, photochemical [2+2] cycloadditions, and nickel-catalyzed intramolecular [4+4] cycloadditions. Transition state force field development will be extended to the MM3 force field. Interesting predictions from these force fields will be studied experimentally in order to establish their predictive utility, or to provide data to correct deficiencies in the force field. We will investigate the scope and limitations of intramolecular reactions using side-chains of different lengths and substitution patterns. The results will be of value as a new tool in the laboratory to aid in the synthesis of natural products and analogs of use in medicinal chemistry.